Interim results of a phase II multicenter study with the oral histone deacetylase inhibitor abexinostat in patients with relapsed/refractory follicular lymphoma.
Authors: Lin Gui, Ying Cheng, Huaqing Wang, Junning Cao, Zhenling Li, Lei Zhang, Yuhuan Gao, Yufu Li, Weijie Xu, Xiang Li, Xiaoyan Ke, Hongmei Jing, Qingyuan Zhang, Yaming Xi, Tingbo Liu, Zhen Wang, Yajie Gao, Qin Pan, Liqun Zou, Yuankai Shi
Journal: Journal of Clinical Oncology (2022)

7513 Background: Follicular lymphoma (FL) is generally considered incurable with patients (pts) often experiencing multiple relapses requiring varying lines of subsequent treatments. Abexinostat (Abx) is a novel potent oral pan- Histone Deacetylase Inhibitor (HDACi) with a pharmacokinetic profile that allows maintenance of sufficient drug concentrations for anti-tumor activity with twice daily (BID) dosing. In prior phase 1/2 studies, Abx was shown to be well-tolerated with significant clinical activity and durable responses in patients with Relapsed/Refractory (R/R) FL. Methods: This open label, single arm study is being conducted to assess the efficacy and safety of Abx in pts with R/R FL. Adults with histologically confirmed grade 1, 2 or 3a FL who have previously received at least 2 lines of therapies, and ECOG PS of 0-2 are being recruited. Abx is administered orally at 80 mg BID 4 hours apart in “one week on, one week off” schedule (Days 1 to 7 &amp; 15 to 21 of a 28-day cycle). Pts undergo efficacy assessment by enhanced CT/MRI every 8 weeks for the first 24 weeks, and every 12 weeks thereafter, and PET-CT at weeks 12 and 24 and to confirm a complete response, in accordance with the Lugano 2014 criteria. The primary endpoint is overall response rate (ORR) assessed by independent review committe (IRC), defined as the % of pts who achieve complete response (CR) or partial response (PR). Secondary endpoints include duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. In a planned interim futility analysis conducted with the first 37 pts, if &lt;12/37 (32%) responded (CR or PR), the study was to be terminated. Results: Between June 17, 2020 and Jan 28, 2022, 41 pts received Abx. 37 pts underwent at least one post baseline tumor assessment. Median age was 55 (range 34 – 79), 46% of pts were male, 70% had stage IV disease and 24% had &gt;3 FLIPI-2. Pts had a median of 3 prior lines of therapy (range 2-6), and 22% were refractory to the last prior treatment. As of the data cutoff date on Jan 31, 2022, of 37 pts evaluable for efficacy, the ORR was 70% (26/37 pts), 16% CR (6/37) and the disease control rate was 92% (34/37). The median time to response was 10.8 weeks. The study has met the pre-defined stage I criteria and has entered stage II, aiming to enroll up to 81 evaluable pts. Of 41 pts evaluable for safety, the most common treatment emergent adverse events (TEAEs) (≥ 30%) were thrombocytopenia (85%), diarrhea (61%), neutropenia (54%), leukopenia (49%), asthenia (39%), nausea (37%), and anemia (34%). Grade ≥ 3 TEAEs (≥ 5%) included thrombocytopenia (41%), neutropenia (27%), leukopenia (7%), lymphopenia (7%), prolonged QT (7%), and anemia (5%). One pt discontinued treatment due to AEs. Conclusions: Oral Abx demonstrated promising efficacy and was well tolerated in patients with R/R FL. Clinical trial information: NCT03934567.